N-ethyl sisomicin

To a solution of 5 g of sisomicin in 250 ml of water add 1 N sulfuric acid until the pH of the solution is adjusted to about 5. To the solution of sisomicin sulfuric acid addition salt thereby formed, add 2 ml of acetaldehyde, stir for 10 minutes, then add 0.B5 g of sodium cyanoborohydride. Continue stirring at room temperature for 15 minutes, then concentrate solution In vacuo to a volume of about 100 ml, treat the solution with a basic ion exchange resin [e.g., Amberlite IRA401S (OH )], then lyophilize to a residue comprising 1-N-ethyl-sisomicin. 

The aminoglycoside sisomicin and its 1-N-ethyl derivative, netilmicin, have been determined in blood and dried blood precolunm derivatization with a-phthalaldehyde and -mercaptopropanoic add and reversed-phases analysis. Dihydrostreptomydn has been used in the exemplification of capillary h.p.Lc.-coaxial continuous flow FAB-m.s.-m.s. in which capillaries independently deliver eluant and FAB matrix to the mjs. source. ... 

Until now sisomicin and verdamicin have been relatively little modified. The 1-N-acyl derivatives could be obtained under controlled pH conditions. They show activity comparable to that of the parent compound l-ethyl-sisomidn (netilmicin) 241 was obtained through reaction with an excess of acetaldehyde and sodium borohydride Netilmicin shows an improved antibacterial spectrum. The hydrogenation of sisomicin gave 5 -epi-gentamicin Cia 236 (dihydrosisomicin) This simple conversion caused a substantial loss of activity. 

Netilmicin is a semisynthetic aminoglycoside antibiotic that is active against gram-negative bacteria. Netilmicin is an ethyl derivative (at the 1-N position of the deoxystreptamine ring) of sisomicin. 

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